Anaphylaxis in Pediatric Patients: Early Recognition and Treatment Are Critical for Best Outcomes

Table of Contents

 

Many cases of anaphylaxis are misdiagnosed or undertreated. This issue offers guidance on the identification of patients with anaphylaxis, including those with atypical presentations, provides evidence-based recommendations for first- and second-line treatment, and discusses guidelines for patient disposition. You will learn:

Clinical criteria for diagnosing patients with anaphylaxis

Common causes of anaphylaxis

Risk factors for biphasic reactions and fatal anaphylaxis

Key historical questions and physical examination findings that help identify patients with anaphylaxis

Which route of epinephrine administration is recommended and the appropriate dosing for pediatric patients

When second-line treatments, such as antihistamines or corticosteroids, can be considered

Guidelines for how long to observe patients in ED and when patients should be admitted

Appropriate disposition of patients with anaphylaxis, including prescribing epinephrine autoinjectors and offering training on how to use them, educating patients and families on avoidance of known offending allergens, and referring the patient to a specialist in allergy immunology

1. Abstract
2. Case Presentations
3. Introduction
4. Critical Appraisal of the Literature
5. Epidemiology
   1. Biphasic Reactions
   2. Fatal Anaphylaxis
6. Etiology and Pathophysiology
   1. Immune-Mediated Hypersensitivity
   2. Nonimmune-Mediated Hypersensitivity
7. Differential Diagnosis
   1. Scombroid Poisoning
   2. Mastocytosis
8. Prehospital Care
9. Emergency Department Evaluation
   1. History
   2. Physical Examination
      1. Atypical Anaphylaxis
10. Diagnostic Studies
11. Treatment
    1. Epinephrine
       1. Intramuscular Epinephrine
       2. Intravenous Epinephrine
       3. Epinephrine Dosing Errors
    2. Antihistamines
    3. Corticosteroids
    4. Airway Management
12. Special Circumstances
    1. Beta Blockers
    2. Exercise-Induced Anaphylaxis
13. Controversies and Cutting Edge
    1. Alternate Routes of Epinephrine Administration
    2. Vasopressin
    3. Extracorporeal Membrane Oxygenation
14. Disposition
    1. Emergency Department Observation
       1. Biphasic Reactions
       2. Fatal Anaphylaxis
    2. Admission
    3. Discharge Medications and Referrals
       1. Epinephrine Autoinjector Doses
       2. Injuries From Epinephrine Autoinjectors
       3. Education on Epinephrine Autoinjector Use
15. Summary
16. Risk Management Pitfalls in the Management of Pediatric Anaphylaxis in the Emergency Department
17. Time- and Cost-Effective Strategies
18. Key Points
19. Case Conclusions
20. Clinical Pathways
    1. Clinical Pathway for Diagnosis of Anaphylaxis in Pediatric Patients
    2. Clinical Pathway for Treatment of Anaphylaxis in Pediatric Patients in the Emergency Department
21. Tables and Figures
    1. Table 1. Relevant Guidelines for the Assessment and Management of Anaphylaxis
    2. Table 2. Clinical Criteria For Diagnosing Anaphylaxis
    3. Table 3. Risk Factors for Biphasic Reactions and Fatal Anaphylaxis
    4. Table 4. Common Causes of Anaphylaxis
    5. Table 5. Differential Diagnosis by Predominant Symptom
    6. Table 6. Expert Guideline Recommendations on Antihistamines for Treatment of Anaphylaxis
    7. Table 7. Expert Guideline Recommendations on Corticosteroids for Treatment of Anaphylaxis
    8. Table 8. Expert Guideline Recommendations on Duration of Observation of Patients With Anaphylaxis
    9. Figure 1. Time to Cardiac Arrest Following Exposure to Triggering Agent
22. References

Abstract

Anaphylaxis is a time-sensitive, clinical diagnosis that is often misdiagnosed because the presenting signs and symptoms are similar to those of other disease processes. This issue reviews the criteria for diagnosing a pediatric patient with anaphylaxis and offers evidence-based recommendations for first- and second-line treatment, including the use of epinephrine, antihistamines, and corticosteroids. Guidance is also provided for the appropriate disposition of patients with anaphylaxis, including prescribing epinephrine autoinjectors and offering training on how to use them, educating patients and families on avoidance of known offending allergens, and referring the patient to a specialist in allergy and immunology.

Case Presentations

A 3-year-old girl with a known peanut allergy arrives to your ED via EMS. The girl was given a cookie by a classmate and immediately developed a generalized urticarial rash. EMS personnel gave her 12.5 mg of oral diphenhydramine and transported her to the ED. On examination, the patient has a heart rate of 160 beats/min with normal oxygenation and perfusion. She has bilateral periorbital swelling, without respiratory distress, wheezing, vomiting, or diarrhea. The accompanying daycare teacher tells you that the girl has previously been admitted to the intensive care unit for anaphylaxis. You call the girl's parents for more information and wonder what to do in the meantime. Is diphenhydramine sufficient treatment for this patient? Are corticosteroids indicated? Is this just an allergic reaction or could it be an anaphylactic reaction? What are the criteria for diagnosis of anaphylaxis? What are the indications for administering epinephrine in patients with anaphylaxis?

Your next patient is an 8-year-old boy with a history of moderate persistent asthma. He presented to the ED via EMS for respiratory distress and wheezing. The patient was walking home from school when he began coughing and felt short of breath. When he arrived home, he was coughing persistently, wheezing, diaphoretic, and red in the face. On arrival to the ED, the patient is given inhaled nebulized albuterol via face mask and is afebrile with the following vital signs: oxygen saturation, 90% on oxygen; heart rate, 150 beats/min; respiratory rate, 38 breaths/min; and blood pressure, 135/80 mm Hg. He appears tired, has moderate retractions with poor aeration on lung examination, bounding pulses, and his skin appears diffusely red and warm. He states he has an egg allergy. He previously had a remote admission for an asthma exacerbation but has not had any surgeries. He had been in good health prior to today. You are concerned that this could be an anaphylactic reaction. What is the best treatment for anaphylaxis? How long should you observe the patient for a biphasic reaction or fatal anaphylaxis?

An otherwise healthy 15-year-old boy is brought to the ED by EMS for a syncopal episode at home. In the past 4 hours, he has had 4 episodes of nonbilious vomiting and 3 episodes of watery, nonbloody diarrhea with crampy abdominal pain. He has not had a fever. The boy’s parents state that he was going to use the restroom after eating dinner, and he fell on his way to the bathroom. EMS administered a 20-mL/kg bolus of normal saline en route to the ED. On arrival to the ED, the patient appears tired and is diaphoretic. His vital signs are as follows: oxygen saturation, 99% on room air; heart rate, 150 beats/min; respiratory rate, 22 breaths/min; blood pressure, 60/40 mm Hg, and temperature, normal. He is able to answer questions, has clear lungs, no abdominal tenderness, and a capillary refill time of 3 to 4 seconds. The boy appears to have normal sinus rhythm on the monitor. His bedside glucose level is 110 mg/dL. The parents deny sick contacts or recent travel history. The patient has no known allergies and is not taking any medications. His vital signs do not improve after a second 20-mL/kg bolus of normal saline. You consider his diagnosis. Is this dehydration from acute gastroenteritis or food poisoning, or perhaps an atypical presentation of anaphylaxis? Are there any labs that can help you decide if this is an anaphylactic reaction? You recall that patients with anaphylaxis can present with gastrointestinal and cardiovascular symptoms, with no skin changes. You decide to administer 0.3 mg of epinephrine IM. The boy's mental status and capillary refill time improve, but he is persistently hypotensive. Should you administer another dose of epinephrine? What are the criteria for admission of a patient with anaphylaxis?

Introduction

An allergic reaction is an overreaction of the immune system to a foreign substance (allergen). Anaphylaxis is a type of an allergic reaction that is an acute, severe systemic hypersensitivity reaction that can rapidly lead to death.¹ The signs and symptoms of anaphylaxis are similar to other common illnesses, which can make diagnosis challenging. Atypical anaphylaxis can be even more difficult to diagnose, because some of the typical signs of anaphylaxis are not present. As such, many cases are misdiagnosed and undertreated.^2-7 Early treatment of anaphylaxis with epinephrine can prevent progression to life-threatening respiratory failure and/or cardiovascular collapse.^1,8-15 All published guidelines recommend early administration of epinephrine for anaphylaxis, even in uncertain cases.^1,11-18 Despite this recommendation, studies suggest that epinephrine remains underutilized by emergency clinicians, and that gaps in knowledge of management of anaphylaxis exist among primary care providers as well.^19,20 Furthermore, patients with anaphylaxis are often misdiagnosed with an “allergic reaction” and given antihistamines and corticosteroids instead of epinephrine.^2,5,7 Recent studies suggest that the incidence of anaphylaxis is increasing globally,^21-26 with an increase in both emergency department (ED) visits and hospitalizations. Pediatricians, first responders, and emergency clinicians should therefore be well versed in the variety of presentations of anaphylaxis and remain vigilant.

This issue of Pediatric Emergency Medicine Practice offers guidance on the identification of patients with anaphylaxis, including those with atypical presentations, reviews recent guidelines and evidence-based recommendations for first-line and second-line anaphylaxis treatment, describes risk factors associated with biphasic anaphylaxis and fatal anaphylaxis, and discusses guidelines for patient disposition.

Critical Appraisal of the Literature

A literature review was performed using the PubMed and Ovid MEDLINE^® databases with the search terms anaphylaxis, allergic reaction, food allergy, drug allergy, anaphylactic shock, epinephrine, adrenaline, antihistamines, glucocorticoids, biphasic reaction, and fatal anaphylaxis. Additionally, the references of each identified article were reviewed for relevant citations. A total of 143 articles from 1985 to the present were chosen for inclusion.

National and international organizations have published guidelines for the diagnosis, management, and treatment of anaphylaxis.^1,8-15 (See Table 1.) In 2011, the World Allergy Organization released anaphylaxis guidelines that have since been updated with current evidence-based recommendations. In 2014, both the International Consensus and the Joint Task Force on Practice Parameters released updated anaphylaxis guidelines and practice parameters. A search of the National Guideline Clearinghouse also yielded a 2014 anaphylaxis guideline from the European Academy of Allergy and Clinical Immunology.

Although there are multiple published guidelines on the recognition and treatment of anaphylaxis, no large randomized controlled trials have been conducted. There are no randomized, placebo-controlled studies of medications used for the treatment of anaphylaxis in adults or children. A search of the Cochrane Database of Systematic Reviews yielded several systematic reviews on anaphylaxis treatment and management: a 2007 review of H1 antihistamines in anaphylaxis,²⁷ a 2009 review of epinephrine,²⁸ a 2012 review of epinephrine autoinjectors,²⁹ and a 2012 review of glucocorticoids.³⁰

The literature on pediatric anaphylaxis is limited, and it is mostly extrapolated from adult studies, retrospective chart reviews, epidemiologic studies, review articles, and case reports. Most studies are retrospective, with associated limitations. Results are difficult to compare because there was no standard definition for anaphylaxis until publication of consensus guidelines in 2006.¹ (See Table 2.) Reported incidence and outcomes vary greatly, likely due to the lack of a standard definition and variability in reporting. When available, studies restricted to pediatric patients were reviewed and included. However, most studies on anaphylaxis include all ages, so pediatric-specific data are not always available, and many of the references in this review involve combined pediatric and adult data. Relevant adult-only studies were included when necessary to supplement limited pediatric data.

Risk Management Pitfalls in the Management of Pediatric Anaphylaxis in the Emergency Department

2. “The patient doesn’t have cutaneous findings, so it can’t be anaphylaxis.”

The diagnosis of anaphylaxis does not require cutaneous findings. Acute onset of any 2 of the systems listed in Table 2 or hypotension after exposure to a known allergen is sufficient for the diagnosis of anaphylaxis. Even in cases of fatal anaphylaxis, patients may lack cutaneous signs, so treatment should not be delayed due to a lack of cutaneous findings.

3. “The epinephrine autoinjector is self-explanatory. I’m busy. He’ll figure it out if he ever needs to use it.”

Clinicians frequently neglect to counsel patients on appropriate epinephrine autoinjector use. Many patients do not know how to use their autoinjectors properly. Time spent teaching a patient how to use the autoinjector may be lifesaving during a future episode of anaphylaxis.

4. “The nurse questioned my IM epinephrine order because he’s always given epinephrine subcutaneously.”

The onset of action of epinephrine is more rapid with IM administration, and expert guidelines recommend IM rather than subcutaneous administration of epinephrine.

Tables and Figures

References

Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of patients. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.

To help the reader judge the strength of each reference, pertinent information about the study is included in bold type following the reference, where available. In addition, the most informative references cited in this paper, as determined by the author, are highlighted.

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